JCI Insight (Jul 2021)

Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation

  • Simona Pagliuca,
  • Carmelo Gurnari,
  • Sanghee Hong,
  • Ran Zhao,
  • Sunisa Kongkiatkamon,
  • Laila Terkawi,
  • Misam Zawit,
  • Yihong Guan,
  • Hassan Awada,
  • Ashwin Kishtagari,
  • Cassandra M. Kerr,
  • Thomas LaFramboise,
  • Bhumika J. Patel,
  • Babal K. Jha,
  • Hetty E. Carraway,
  • Valeria Visconte,
  • Navneet S. Majhail,
  • Betty K. Hamilton,
  • Jaroslaw P. Maciejewski

Journal volume & issue
Vol. 6, no. 13

Abstract

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TCR repertoire diversification constitutes a foundation for successful immune reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT). Deep TCR Vβ sequencing of 135 serial specimens from a cohort of 35 allo-HCT recipients/donors was performed to dissect posttransplant TCR architecture and dynamics. Paired analysis of clonotypic repertoires showed a minimal overlap with donor expansions. Rarefied and hyperexpanded clonotypic patterns were hallmarks of T cell reconstitution and influenced clinical outcomes. Donor and pretransplant TCR diversity as well as divergence of class I human leukocyte antigen genotypes were major predictors of recipient TCR repertoire recovery. Complementary determining region 3–based specificity spectrum analysis indicated a predominant expansion of pathogen- and tumor-associated clonotypes in the late post–allo-HCT phase, while autoreactive clones were more expanded in the case of graft-versus-host disease occurrence. These findings shed light on post–allo-HCT adaptive immune reconstitution processes and possibly help in tracking alloreactive responses.

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